Evidence From Humans
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Case-control study of breast cancer and exposure to synthetic environmental chemicals among Alaska Native women
Holmes, A. K., Koller, K. R., Kieszak, S. M., Sjodin, A., Calafat, A. M., Sacco, F. D., Varner, D. W., Lanier, A. P., Rubin, C. H. Int J Circumpolar Health. 2014. 73, 25760.
Topic area
Environmental pollutant - DDT PCBs PBDE Phthalates
Study design
Hospital based case-control
Funding agency
Not reported
Study Participants
Menopausal Status
The menopausal status of women included in this study is listed here.
No analyses based on menopausal status
Number of Controls
Controls: 95
Participant selection: Inclusion and exclusion criteria
Criteria used to select participants in the study.
Participants were primarily Eskimo, Indian, Aleut women who came to Alaska Native Medical Center for breast biopsy, lumpectomy, mastectomy or breast reconstruction between 1999-2002. Cases were pathologically confirmed cases of invasive or in situ breast cancer. Controls were those whose pathology reports were negative for cancer, but had diagnoses of benign breast conditions. Women were 30-88 years old at enrollment.
Comment about participation selection
Controls with benign breast disease may not be appropriate since they are at higher risk of developing breast cancer.
Exposure Investigated
Exposures investigated
Lipid-adjusted serum concentrations of p,p'-DDE, HCB, mirex, oxychlordane, β-HCH, γ-HCH, o,p'-DDT, p,p'-DDT, trans-Nonachlor, PCBs 138/158, PCB 153, PCB 180 and BDE-47, and creatinine-adjusted urine concentrations of MBP, MBzP, MEHHP, MEHP, MEOHP, MEP a
Exposure assessment comment
The PCBs included in the analysis are considered to come primarily from diet.
Breast cancer outcome investigated
Primary incident breast cancer
Ethnic groups with separate analysis
If this study provided a separate analysis by ethnic or racial group, the groups are listed here.
Eskimo (54.7%), Indian (21.8%), Aleut (15.9%), Other (7.6%)
Confounders considered
Other breast cancer risk factors, such as family history, age at first birth, and hormone replacement therapy use, that were taken into account in the study.
Age, ethnicity, smoking and alcohol history, family history of breast cancer, number of live births, breastfeeding history, menopausal status, hormone use history.
Genetic characterization included
If the study analyzed relationships between environmental factors and inherited genetic variations, this field will be marked Yes. No, if not.
Strength of associations reported
Persistent pesticides, (ng/g lipid):
p,p'-DDE: OR 0.60 (95% CI 0.26-1.43)
Hexachlorobenzene: OR 0.47 (95% CI 0.19-1.16)
Mirex: OR 0.65 (95% CI 0.28-1.55)
Oxychlordane: OR 0.91 (95% CI 0.3-2.35)
β-HCH: OR 1.21 (95% CI 0.44-3.31)
γ-HCH: OR 1.88 (95% CI 0.88-4.03)
o,p'-DDT: OR 1.00 (95% CI 0.48-2.11)
p,p'-DDT: OR 0.49 (95% CI 0.22-1.10)
trans-Nonachlor: OR 0.65 (95% CI 0.26-1.66)

PCBs (ng/g lipid):
138/158: OR 0.64 (95% CI 0.27-1.52)
153: OR 0.55 (95% CI 0.22-1.41)
180: OR 0.43 (95% CI 0.17-1.09)

PBDE-47 (ng/g lipid): OR 1.58 (95% CI 0.75-3.33)

Phthalate metabolites, (ug/g creatinine):
Mono-butyl phthalate (MBP): OR 0.66 (95% CI 0.32-1.39)
Mono-benzyl phthalate (MBzP): OR 1.53 (95% CI 0.73-3.22)
Mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP): OR 1.50 (95% CI 0.71-3.17)
Mono-(2-ethylhexyl) phthalate (MEHP): OR 2.43 (95% CI 1.12-5.24)
Mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP): OR 1.15 (95% CI 0.54-2.44)
Mono-ethyl phthalate (MEP): OR 0.55 (95% CI 0.26-1.18)
Mono-methyl phthalate (MMP): OR 0.86 (95% CI 0.40-1.85)
Results Comments
Geometric mean BDE-47 concentration did not significantly differ between ER+/PR+ and ER-/PRcases. ER-/PR- cases tended to have higher geometric mean concentrations of the congeners and congener ratio compared to ER+/PR+ cases, but none of the differences were significant. These analyses were not controlled for confounding. Because creatinine levels can vary by dietary protein, adjusting phthalate measurements for creatinine may obscure dietary exposures, such as phthalates in packaged meat.
Author address
Health Studies Branch, Division of Environmental Hazards and Health Effects, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA; aoh8@cdc.gov. Office of Alaska Native Health Research, Division of Communi
Reviewers Comments
This is one of the few studies that examines PBDEs and breast cancer risk. This study included Eskimo, Indian, and Aleut women who historically have low breast cancer risk, but are of interest because global fate and transport results in higher concentrations of persistent chemicals in the Arctic.
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